A multi-institutional phase II study of BMS-182248-01 (BR96-doxorubicin conjugate) administered every 21 days in patients with advanced gastric adenocarcinoma.

PURPOSE: High levels (> 200,000 molecules per carcinoma cell) of the LewisY antigen are expressed on the surface of most (> 75%) gastric carcinomas. The BMS-182248-01 is a chimeric variant of anti-LewisY monoclonal antibody that is conjugated with doxorubicin. In a phase I study, BMS-182248-01 resulted in a partial response in a patient with gastric carcinoma. We, therefore, conducted a multi-institutional phase II study of BMS-182248-01 in patients with advanced gastric carcinoma. METHODS AND PATIENTS: Only patients with evidence of LewisY antigen by immunohistochemical method on their gastric carcinoma were treated. Patients with unresectable gastric adenocarcinoma were eligible. Patients had to have adequate liver, renal, and marrow functions. Written consent was obtained from all patients. All patients were hospitalized. BMS-182248-01 was administered at the starting dose of 700 mg/m2 i.v. over 24 hours on day 1 every 3 weeks. RESULTS: Fifteen patients were enrolled. There were 10 men and 5 women. The median age at enrollment was 56 years, with ages ranging from 34 to 80 years. No objective responses were observed. Five patients had disease stabilization. The remaining 10 patients progressed on study. Rapidly reversible gastrointestinal toxicity, primarily nausea and emesis, was predominant. There was no neutropenia, thrombocytopenia, or cardiomyopathy. CONCLUSIONS: Although BMS-182248-01 represents a novel approach of monoclonal antibody conjugated with an active chemotherapy agent, delivered intracellularly, it was ineffective in patients with gastric carcinoma whose tumors carried LewisY antigen.

Enhanced staging and all chemotherapy preoperatively in patients with potentially resectable gastric carcinoma.

PURPOSE: Patients with local-regional gastric carcinoma have a low rate of curative resection (R0) because of the advanced stage at diagnosis and suboptimal clinical staging. This study was designed to improve clinical staging with the use of laparoscopy and endoscopic ultrasonography (EUS) and to improve R0 resection rates and tolerance by delivering all chemotherapy preoperatively in patients with potentially resectable gastric carcinoma. PATIENTS AND METHODS: All patients with histologic proof of localized adenocarcinoma of the stomach underwent a staging laparoscopy before registration. EUS was performed when feasible. The intention was to administer up to five courses of preoperative chemotherapy consisting of fluorouracil (500 mg/m(2)/d as a continuous infusion on days 1 through 5 and as a bolus on days 12 and 19), interferon alfa-2b (3 million units subcutaneously three times a week for 3 weeks), and cisplatin (15 mg/m(2)/d as a bolus on days 1 through 5). After chemotherapy, surgery was attempted to remove the primary and regional lymph nodes. Clinical response and EUS staging were correlated with surgical pathology. The feasibility of this approach, resection rates, patient survival, and patterns of failure also were assessed. RESULTS: All 30 patients enrolled were assessed for toxicity, response, and survival. Nineteen men and 11 women were enrolled. The median number of courses delivered per patient was three (range, one to five courses). Fourteen patients (47%) received all five preoperative courses of chemotherapy. The overall clinical response rate was 34%. Twenty-nine patients (97%) underwent attempted resection. Twenty-five (83%) had an R0 resection. Two patients (7%) had no evidence of carcinoma in the surgical specimen, and three had only microscopic carcinoma (>/= 90% necrosis). Posttreatment EUS findings did not correlate well with surgical pathology. The median duration of follow-up was 30 months (range, 5 months to 65+ months). The median survival time for 30 patients, calculated by the Kaplan-Meier method, was 30 months (range, 5 months to 65+ months). There were no cases of grade 4 toxicity. CONCLUSION: It is feasible to administer prolonged preoperative therapy in patients with potentially resectable gastric carcinoma. Enhanced staging with laparoscopy and EUS helped in proper selection of patients and better characterization of the stage.